ArticleJournal for immunotherapy of cancer2025
C5a/C5aR pathway blocking promoted CuS-mediated cancer therapy effect by inhibiting cuproptosis resistance.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- SOX2 Inhibits Cuproptosis to Affect Cisplatin Resistance in Non-Small Cell Lung Cancer by Activating the Wnt/ATP7B Signaling Pathway.The Kaohsiung journal of medical sciences · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Review
- Cuproptosis: Biomarkers, Mechanisms and Treatments in Diseases.Molecules (Basel, Switzerland) · 2026Review
- Article
- Targeting innate immunity to modulate bone metabolism: a novel strategy for osteoporosis treatment.Frontiers in aging · 2026Review
- Advances in Versatile Copper Sulfide-Based Nanoplatforms: From Synthesis and Properties to Multifaceted Biomedical Applications.International journal of nanomedicine · 2026Review
- Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance.Molecular cancer · 2025Review
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Authors and funding
11 authors.
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Abstract
backgroundBreast cancer is the most diagnosed malignancy and a leading cause of cancer-related deaths among women globally. Cuproptosis plays a significant role in tumor progression and therapeutic response. Increasing studies suggest that targeting cuproptosis presents a promising strategy for cancer therapy, such as through the development of copper nanoparticles as therapeutic agents. However, resistance to cuproptosis has emerged as a critical hallmark of cancer. Therefore, it is essential to further investigate the mechanisms underlying cuproptosis resistance to enhance its therapy effect.
methodsThe relationship between breast cancer progression and the C5a/C5aR pathway or cuproptosis was determined by single-cell RNA sequencing analyses, RNA-sequence analyses, bioinformatic analyses, survival analyses and immunohistochemistry. The antitumor effects of CuS nanoparticles and C5a receptor antagonists (C5aRA) were assessed by in vitro and in vivo strategies including cell counting kit-8, colony formation assay, relative reactive oxygen species level assay, western blots, real-time quantitative PCR, immunohistochemistry, immunofluorescence assay, flow cytometry and the xenograft mice models. Complement system activation by CuS nanoparticles was tested by ELISA.
resultsOur results indicated that activation of the C5a/C5aR pathway contributes to cuproptosis resistance by upregulating ATP7B expression via the Wnt/β-catenin pathway. Consequently, combining CuS nanoparticles with lazer treatment and C5aRA markedly enhanced the antitumor efficacy of CuS nanoparticles by overcoming cuproptosis resistance, leading to a synergistic effect in cancer therapy that included cuproptosis-targeting therapy, immunotherapy, and photothermal therapy.
conclusionsThis study reports, for the first time, proved C5a/C5aR pathway-mediated cuproptosis resistance in cancer cells, and combining CuS nanoparticles and C5aRA offers a superior and novel therapeutic strategy for cancer.
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